{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:43:58Z","timestamp":1790034238333,"version":"4.0.1"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T00:00:00Z","timestamp":1619654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Metabolic acidosis is a common complication of chronic kidney disease (CKD). Veverimer is an orally administrated, free amine polymer with high capacity and binding selectivity to hydrochloric acid from the gastrointestinal tract. This study pooled the current evidence of the efficacy and safety of veverimer for the treatment of metabolic acidosis associated with CKD. We conducted a systematic literature search on PubMed, Embase, and Cochrane Central for relevant randomized controlled trials (RCTs) in June 2020. In this study, three RCTs with 548 patients were included in our analysis. The analysis revealed that veverimer was associated with increased bicarbonate level of patients (weight mean difference [WMD] 3.08, 95% confidence interval [CI] [2.40, 3.77], <jats:italic>p<\/jats:italic> &amp;lt; 0.001) and improved physical function compared with placebo measured by Kidney Disease and Quality of Life Short Form 36, question 3 (physical functioning domain) (KDQoL-PFD) score (WMD 5.25, 95% CI [1.58, 8.92], <jats:italic>p<\/jats:italic> = 0.005). For safety outcomes, both groups exhibited similar risks for developing headache, diarrhea, flatulence, and hyperkalemia. In conclusion, current clinical evidence indicates that veverimer is efficacious and safe against metabolic acidosis related to CKD compared with placebo. Further research comparing long-term veverimer use with traditional alkali therapy is needed.<\/jats:p>","DOI":"10.3389\/fphar.2021.643128","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T12:51:01Z","timestamp":1619700661000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Efficacy and Safety of Veverimer in the Treatment of Metabolic Acidosis Caused by Chronic Kidney Disease: A Meta-analysis"],"prefix":"10.3389","volume":"12","author":[{"given":"Wenlin","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haonan","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaomiao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"714","DOI":"10.2215\/cjn.08340812","article-title":"Effects of Oral Sodium Bicarbonate in Patients with CKD","volume":"8","author":"Abramowitz","year":"2013","journal-title":"Cjasn"},{"key":"B2","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1053\/j.ajkd.2020.07.019","article-title":"Veverimer: An Emerging Potential Treatment Option for Managing the Metabolic Acidosis of CKD","volume":"76","author":"Adrogu\u00e9","year":"2020","journal-title":"Am. J. Kidney Dis."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.1592\/phco.2005.25.12.1687","article-title":"Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease: an Overview","volume":"25","author":"Bailie","year":"2005","journal-title":"Pharmacotherapy"},{"key":"B4","doi-asserted-by":"publisher","first-page":"26","DOI":"10.2215\/CJN.07300717","article-title":"Randomized, Controlled Trial of TRC101 to Increase Serum Bicarbonate in Patients with CKD","volume":"13","author":"Bushinsky","year":"2018","journal-title":"Cjasn"},{"key":"B5","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1097\/MNH.0000000000000524","article-title":"Advances in Management of Chronic Metabolic Acidosis in Chronic Kidney Disease","volume":"28","author":"Chen","year":"2019","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1001\/archinternmed.2009.112","article-title":"The Impact of Selecting a High Hemoglobin Target Level on Health-Related Quality of Life for Patients with Chronic Kidney Disease","volume":"169","author":"Clement","year":"2009","journal-title":"Arch. Intern. Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"472","DOI":"10.7326\/m15-1839","article-title":"The Effect of Erythropoietin-Stimulating Agents on Health-Related Quality of Life in Anemia of Chronic Kidney Disease","volume":"164","author":"Collister","year":"2016","journal-title":"Ann. Intern. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1007\/s40620-019-00656-5","article-title":"Treatment of Metabolic Acidosis with Sodium Bicarbonate Delays Progression of Chronic Kidney Disease: the UBI Study","volume":"32","author":"Di Iorio","year":"2019","journal-title":"J. Nephrol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1053\/j.ajkd.2013.01.017","article-title":"Association of Serum Bicarbonate with Risk of Renal and Cardiovascular Outcomes in CKD: a Report from the Chronic Renal Insufficiency Cohort (CRIC) Study","volume":"62","author":"Dobre","year":"2013","journal-title":"Am. J. Kidney Dis."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e001599","DOI":"10.1161\/JAHA.114.001599","article-title":"Persistent High Serum Bicarbonate and the Risk of Heart Failure in Patients with Chronic Kidney Disease (CKD): A Report from the Chronic Renal Insufficiency Cohort (CRIC) Study","volume":"4","author":"Dobre","year":"2015","journal-title":"Jaha"},{"key":"B11","doi-asserted-by":"publisher","first-page":"Itc1","DOI":"10.7326\/aitc201506020","article-title":"Chronic Kidney Disease","volume":"162","author":"Drawz","year":"2015","journal-title":"Ann. Intern. Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1053\/j.ajkd.2014.05.009","article-title":"Serum Bicarbonate Concentrations and Kidney Disease Progression in Community-Living Elders: the Health, Aging, and Body Composition (Health ABC) Study","volume":"64","author":"Goldenstein","year":"2014","journal-title":"Am. J. Kidney Dis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.21037\/atm-20-3320","article-title":"Veverimer for Treatment of Chronic Metabolic Acidosis in Patients with Chronic Kidney Disease","volume":"8","author":"Gone","year":"2020","journal-title":"Ann. Transl Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1038\/ki.2012.74","article-title":"Moderation of Dietary Sodium Potentiates the Renal and Cardiovascular Protective Effects of Angiotensin Receptor Blockers","volume":"82","author":"Heerspink","year":"2012","journal-title":"Kidney Int."},{"key":"B15","doi-asserted-by":"publisher","first-page":"d5928","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane Collaboration's Tool for Assessing Risk of Bias in Randomised Trials","volume":"343","author":"Higgins","year":"2011","journal-title":"BMJ"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e0158765","DOI":"10.1371\/journal.pone.0158765","article-title":"Global Prevalence of Chronic Kidney Disease - A Systematic Review and Meta-Analysis","volume":"11","author":"Hill","year":"2016","journal-title":"PLoS One"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.2215\/cjn.00380118","article-title":"Effect of Treatment of Metabolic Acidosis on Vascular Endothelial Function in Patients with CKD","volume":"13","author":"Kendrick","year":"2018","journal-title":"Cjasn"},{"key":"B18","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1124\/jpet.120.000190","article-title":"Mechanism of Action of Veverimer: A Novel, Orally Administered, Nonabsorbed, Counterion-free, Hydrochloric Acid Binder under Development for the Treatment of Metabolic Acidosis in Chronic Kidney Disease","volume":"375","author":"Klaerner","year":"2020","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B19","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1053\/j.ajkd.2015.08.028","article-title":"Metabolic Acidosis of CKD: An Update","volume":"67","author":"Kraut","year":"2016","journal-title":"Am. J. Kidney Dis."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1038\/sj.ki.5000297","article-title":"Chemical and Hormonal Determinants of Vascular Calcification In Vitro","volume":"69","author":"Lomashvili","year":"2006","journal-title":"Kidney Int."},{"key":"B21","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1053\/j.ajkd.2010.03.023","article-title":"Serum Bicarbonate and Long-Term Outcomes in CKD","volume":"56","author":"Menon","year":"2010","journal-title":"Am. J. Kidney Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e1000097","DOI":"10.1371\/journal.pmed.1000097","article-title":"Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA Statement","volume":"6","author":"Moher","year":"2009","journal-title":"Plos Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.2215\/CJN.13091118","article-title":"Effects of Treatment of Metabolic Acidosis in CKD","volume":"14","author":"Navaneethan","year":"2019","journal-title":"Cjasn"},{"key":"B24","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1186\/s12882-019-1309-y","article-title":"Self-management Interventions for Chronic Kidney Disease: a Systematic Review and Meta-Analysis","volume":"20","author":"Peng","year":"2019","journal-title":"BMC Nephrol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1053\/j.ajkd.2019.01.036","article-title":"Metabolic Acidosis in CKD: Core Curriculum 2019","volume":"74","author":"Raphael","year":"2019","journal-title":"Am. J. Kidney Dis."},{"key":"B26","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1038\/ki.2010.388","article-title":"Higher Serum Bicarbonate Levels within the Normal Range Are Associated with Better Survival and Renal Outcomes in African Americans","volume":"79","author":"Raphael","year":"2011","journal-title":"Kidney Int."},{"key":"B27","doi-asserted-by":"publisher","first-page":"141","DOI":"10.2165\/00019053-199915020-00003","article-title":"Determining Clinically Important Differences in Health Status Measures","volume":"15","author":"Samsa","year":"1999","journal-title":"Pharmacoeconomics"},{"key":"B28","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1053\/j.ajkd.2009.02.014","article-title":"Serum Bicarbonate Levels and the Progression of Kidney Disease: a Cohort Study","volume":"54","author":"Shah","year":"2009","journal-title":"Am. J. Kidney Dis."},{"key":"B29","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1159\/000339329","article-title":"Short- and Long-Term Effects of Alkali Therapy in Chronic Kidney Disease: a Systematic Review","volume":"35","author":"Susantitaphong","year":"2012","journal-title":"Am. J. Nephrol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/s0140-6736(19)31388-1","article-title":"Long-term Safety and Efficacy of Veverimer in Patients with Metabolic Acidosis in Chronic Kidney Disease: a Multicentre, Randomised, Blinded, Placebo-Controlled, 40-week Extension","volume":"394","author":"Wesson","year":"","journal-title":"The Lancet"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1016\/s0140-6736(18)32562-5","article-title":"Veverimer versus Placebo in Patients with Metabolic Acidosis Associated with Chronic Kidney Disease: a Multicentre, Randomised, Double-Blind, Controlled, Phase 3 Trial","volume":"393","author":"Wesson","year":"","journal-title":"The Lancet"},{"key":"B32","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1186\/s13063-015-0843-6","article-title":"Does Oral Sodium Bicarbonate Therapy Improve Function and Quality of Life in Older Patients with Chronic Kidney Disease and Low-Grade Acidosis (The BiCARB Trial)? Study Protocol for a Randomized Controlled Trial","volume":"16","author":"Witham","year":"2015","journal-title":"Trials"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.643128\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T12:51:03Z","timestamp":1619700663000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.643128\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,29]]},"references-count":32,"alternative-id":["10.3389\/fphar.2021.643128"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2021.643128","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,29]]},"article-number":"643128"}}